Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2022—Organic macromolecular compounds
  • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2013—Organic compounds, e.g. phospholipids, fats
  • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2095—Tabletting processes

Definitions

• This invention relates to fast dissolving dosage forms for oral administration containing a chemical, such as a pharmaceutical, substance and which dissolve, for example, in the mouth within 10 seconds. More particularly, this invention relates to an improvement in such dosage forms wherein the open matrix structure comprises mainly mannitol.
• Fast dissolving dosage forms are known in the art and are desribed in U.S. Letters Pat. No. 4,371,516 issued Feb. 1, 1983.
• the dosage forms are described as providing a shaped article carrying a chemical, the article being capable of being rapidly disintegrated by water and comprising an open matrix network carrying the chemical, the open matrix network being comprised of a water-soluble or water-dispersible carrier material that is inert towards the chemical.
• the carrier material described as being particularly advantageous is gelatin which has been partially hydrolysed by heating a solution of gelatin in water e.g. in an autoclave at about 120° C. for from about 5-60 minutes.
• This invention is an improved pharmaceutical dosage form for oral administration as a solid, which dosage form can be disintegrated by water within ten seconds and which consists essentially of an open matrix network carrying a unit dosage of a pharmaceutical susbstance, the open matrix network consisting essentially of a pharmacologically acceptable water-soluble or water-dispersible carrier material, and the improvement comprising selecting the carrier material from the group consisting essentially of mannitol in admixture with a natural gum, preferably acacia, guar gum, xanthan gum and tragacanth gum.
• suitable natural gums include locust bean gum, pectin, algin, agar, carrageenan and gum arabic.
• the mannitol constitutes at least about 10% by weight of the final dosing suspension and no more than about 15% by weight.
• the pharmaceutical substance is chlorpheniramine maleate and the natural gum component is a mixture of guar gum and acacia gum.
• the formulation for the dosage form is as follows:
• portion A The deionized water was divided in a one-third portion, designated portion A, and a two-thirds portion, portion B.
• Portion A was heated to 75° C. and the methylparaben and propyparaben were added slowly with stirring until dissolved. Separately the colloidal silicon dioxide was added to portion B and stirred until evenly dispersed. Portion A was then added to portion B. The temperature of the mixture rose to 30-40° C. Then added separately with stirring until dissolved were mannitol grannules, the pregelatinized starch, Nutrasweet, chlorpheniramine maleate, acacia gum, and guar gum.
• the freeze drier employed in this example was a Virtis 25 SRC Model Freeze Drier.
• the fast dissolving dosage forms were prepared by dosing 500 milligrams of the suspension into each well in a thermoformed blister tray containing 10 wells per tray. The filled trays were placed in a larger tray containing a dry ice-methanol mixture.
• the samples were placed on the freeze dryer trays at a shelf temperature of -45° C.
• the condenser was turned on and the freezer turned off. The condenser temperature was brought to between -40 and -45° C.
• the heat-dry cycle lasted for 3 hours.
• the vacuum, the condenser and the heater were turned off and the samples removed.
• the wafers from each batch were removed from the wells in the trays. They were white in color and each weighed about 105 milligrams of which about 40 milligrams was chlorpheniramine. The wafers were crisp, when placed on the tongue exhibited a good flavor and disintegrated rapidly. When placed in water at 37° C., the wafers dissolved in less than 10 seconds.
• a second medication in addition to chlorpheniramine, a second medication, phenylephrine, is added to the formulation.
• the wafers had good body (snap/crispness) and the disintegration time was less than 10 seconds in water at 37° C.
• the formulation is presented below and the procedure for its preparation is essentially the same as described in Example 1.
• the mannitol and the gum provide the structure of the wafer, the gum serving as a binding agent, and the starch serves as a wicking agent to aid in dissolution.
• the amount of mannitol can vary from about 10% to about 16% by weight of the precursor liquid formulation. Amounts as high as 17.5% and 20% by weight have been tried but appear to serve no useful purpose, the increased mannitol content improving firmness but decreasing the disintegration time. The about 10% to about 16% by weight of the precursor liquid formulation calculates to about 50% to about 86% of the solid wafer dosage form.
• the amount of gum can vary from 0.7 to 3.2% by weight of the formulation depending upon the type of gum used.
• the dosage forms of the invention advantageously are prepared in a thermoformed blister tray which is sealed with an aluminum foil cover after the freeze-drying procedure.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Epidemiology (AREA)
• Medicinal Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Biophysics (AREA)
• Molecular Biology (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Micro-Organisms Or Cultivation Processes Thereof (AREA)
• Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Priority Applications (10)

Applications Claiming Priority (1)

Publications (1)

Family

ID=23451975

Family Applications (1)

Country Status (10)

Cited By (53)

Citations (11)

Family Cites Families (8)

• 1989
  • 1989-06-20 US US07/368,612 patent/US4946684A/en not_active Expired - Lifetime
• 1990
  • 1990-06-18 CA CA002019228A patent/CA2019228A1/en not_active Abandoned
  • 1990-06-18 PT PT94395A patent/PT94395B/pt not_active IP Right Cessation
  • 1990-06-19 IE IE221690A patent/IE63834B1/en not_active IP Right Cessation
  • 1990-06-19 EP EP19900306632 patent/EP0404490B1/de not_active Expired - Lifetime
  • 1990-06-19 MX MX2121890A patent/MX21218A/es unknown
  • 1990-06-19 AT AT90306632T patent/ATE91409T1/de not_active IP Right Cessation
  • 1990-06-19 ES ES90306632T patent/ES2057409T3/es not_active Expired - Lifetime
  • 1990-06-19 DE DE90306632T patent/DE69002198T2/de not_active Expired - Fee Related
  • 1990-06-19 DK DK90306632.2T patent/DK0404490T3/da active

Patent Citations (11)

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